In vertebrates, skeletal mass is determined by continuous remodeling consisting of the concerted and balanced action of osteoclasts, the bone resorbing cells, and osteoblasts, the bone forming cells. Osteoporosis, the most prevalent degenerative disease in developed countries, results from the impairment of this balance, leading to bone loss and increased fracture risk. Bone remodeling is regulated by a complex convergence of circulating hormones including sex steroids, parathyroid hormone and pituitary-derived thyroid and follicle stimulating hormones, on one hand, and local regulators of bone cell activity such as bone morphogenetic proteins, receptor activators of nuclear factor κB ligand (RANKL) and a number of cytokines, on the other hand [Abe et al, 2003; Sun et al, 2006; Rosen, 2006; Robling et al, 2006].
Recent work has shown that neuroendocrine pathways and neurotransmitters also have a key role in the regulation of bone remodeling [Takeda et al, 2002; Elefteriou et al, 2005; Lin et al, 2004; Allison and Herzog, 2006; Patel and Elefteriou, 2007; Tam et al, 2008]. Upon finding of a skeletal endocannabinoid system [Bab, 2005; Idris et al, 2005; Karsak et al, 2005; Ofek et al, 2006, Tam et al, 2006, Tam et al, 2008; Scutt and Williamson, 2007; Bab, 2007; Bab and Zimmer, 2008], it was particularly shown that arachidonoyl ethanolamide (anandamide, AEA) [Devane et al., 1992] and 2-archidonoylglycerol (2-AG) [Mechoulam et al, 1995] are present in bone tissue. Furthermore, N-arachidonoyl-serine (ARA-S), a mitogenically active compound, which is structurally related to endocannabinoids was identified in the brain [Milman et al, 2006].
There is a growing need in aging modern society for potent and stable compositions capable of promoting bone cell formation in order to achieve better treatment of medical conditions associated with bone tissue loss.